- Shell cross-linked nanoparticles designed to target angiogenic blood vessels via αvβ3 receptor-ligand interactions
-
The design, synthesis, and characterization of a novel polymeric nanostructured material bearing surface-attached integrin antagonists are demonstrated. The covalent coupling of a complex and biologically active small molecule to a well-defined nanostructured material combines the elegance of synthetic organic chemistry with the state-of-the-art polymer chemistry. This unique material offers potential in targeting to tumor neovasculature and delivery of diagnostic and therapeutic agents.
- Pan, Dipanjan,Turner, Jeffrey L.,Wooley, Karen L.
-
-
Read Online
- Polyacrylamides bearing pendant α-sialoside groups strongly inhibit agglutination of erythrocytes by influenza virus: The strong inhibition reflects enhanced binding through cooperative polyvalent interactions
-
An ELISA assay is described for measuring the binding of influenza virus A-X31 to α-sialoside groups that are linked to biotin-labeled polyacrylamides. The efficacy of these polymers in inhibiting the adhesion of influenza virus to erythrocytes (as measured by a hemagglutination assay) was shown to be directly related to the binding affinity of the polymers for the viral surface: the differences in inhibitory efficacy among the polymeric inhibitors and monomeric α-methyl sialoside, among fractions of a polymeric, polyvalent inhibitor with narrow molecular weight ranges, and among polymeric inhibitors prepared by copolymerization or modification of a preformed polymer chain, all correlated with differences in the affinity of the inhibitors for the surface of the virus. The polymeric inhibitors studied had affinities for the viral surface that ranged between 103 and >106 greater than α-methyl sialoside, on the basis of total sialic acid groups in solution. The role of steric stabilization in the mechanism by which these polymers inhibit hemagglutination was investigated. The ability of the polymeric, polyvalent inhibitors to inhibit the binding of a polyclonal antibody to the viral surface suggests that steric stabilization may also be an important effect in this system.
- Sigal,Mammen,Dahmann,Whitesides
-
-
Read Online
- A cholesterol-based tether for creating photopatterned lipid membrane arrays on both a silica and gold surface
-
We report a new cholesterolbased self-assembled monolayer (SAM) for use in attaching lipid membranes to both gold and silica surfaces that can be patterned by deep UV (254 nm) photolysis. It allows essentially equivalent patterned supported bilayers to be created both on gold for impedance studies and on silica for fluorescence studies. On either surface an amine-functionalised SAM is reacted with an N-hydroxysuccinimidylcarbonyl-functionalised E03-cholesteryl derivative. The formation of the aminefunctionalised SAM and its reaction with the E03-cholesteryl derivative were followed by contact-angle measurements, ellipsometry and X-ray pho-toelectron spectroscopy. The resultant layer of cholesterol tethers was patterned by deep UV photolysis, which regenerates the original SiO2 surface in exposed regions on a silica substrate and oxidises thiol groups on a gold substrate. This patterned surface containing hydrophilic SiO2 (or -OH groups) and hydrophobic cholesterol tether regions can be converted to a surface patterned with supported lipid bi- and monolayers (respectively) by immersing in a solution of small unilamellar vesicles of egg yolk phosphatidycholine. The formation of the lipid bi- and monolayer regions on the silica surface was evidenced by fluorescence microscopy. Crucially the bilayer regions remain fully fluid yielding lipid mobilities comparable to those found in physisorbed bilayers. Furthermore charged fluorescent lipids are shown to migrate in an applied field thus providing a platform for the studying the electrophoresis (potentially) for a wide range of charged membrane components, such as membrane proteins. The formation of the patterned lipid membrane on the gold surface was confirmed by electrochemical impedance measurements.
- Han, Xiaojun,Achalkumar, Ammathnadu S.,Bushby, Richard J.,Evans, Stephen D.
-
-
Read Online
- Host–Guest Complexes of Cyclodextrins and Nanodiamonds as a Strong Non-Covalent Binding Motif for Self-Assembled Nanomaterials
-
We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host–guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. We found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantane as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host–guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV.
- Schibilla, Frauke,Voskuhl, Jens,Fokina, Natalie A.,Dahl, Jeremy E. P.,Schreiner, Peter R.,Ravoo, Bart Jan
-
-
Read Online
- Evaluation of the synthesis of sialic Acid-PAMAM glycodendrimers without the use of sugar protecting Groups, and the Anti-HIV-1 properties of these compounds
-
A study was undertaken to evaluate the feasibility of synthesizing six sialic acid-PAMAM glycodendrimers using unprotected sialic acid in as few as 1-4 steps using two different reaction pathways, and to assess the sulfated derivatives for anti-HIV activity. The syntheses were accomplished through either the direct attachment of the sialic acid carboxyl group to amine-terminated PAMAM (a divergent-like approach) using BOP coupling, or by first reacting sialic acid with a polar bifunctional spacer molecule, attaching the sugar-linker to carboxy-terminated PAMAM (a convergent-like approach), and again using BOP-mediated coupling reactions. It was hypothesized that the latter approach would be the most successful method, as any steric congestion between the sialic acid and the PAMAM would be minimized using an intervening polar linker. However, the divergent-like synthesis proved to be the superior method, resulting in 11.4%, 14%, and 28% of the fully substituted generations 0, 1, and 2 sialic acid-PAMAM conjugates, respectively, as compared to 6.4% of only the generation ?0.5 sialic acid-linker-PAMAM conjugate for the convergent-like method. Upon sulfation of the four glycodendrimers, binding capabilities to the recombinant HIV protein, gp120, were assessed using an ELISA assay. Compounds that showed promising binding characteristics were then further assessed for inhibition of HIV-1 infection using a well-characterized luciferase reporter gene neutralization assay. The generation 2 sulfated sialic acid-PAMAM glycodendrimer, sulfo-6, bearing 16 sialic acids with 11 sulfate groups incorporated at 4.03% sulfur content by weight, was found to inhibit all four HIV-1 strains tested in the low micromolar range.
- Clayton, Russell,Hardman, Janee,Labranche, Celia C.,McReynolds, Katherine D.
-
-
Read Online
- Strong positive cooperativity in binding to the A3T3 repeat by Hoechst 33258 derivatives attaching the quinoline units at the end of a branched linker
-
Hoechst 33258 derivatives with additional interacting moieties attached at the ends of branched linkers were synthesized, and their DNA binding properties were investigated with regard to the A3T3 repeat by measuring fluorescence spectra. The binding prop
- Koda, Hironori,Brazier, John Alan,Onishi, Ippei,Sasaki, Shigeki
-
-
Read Online
- A Specific and Covalent JNK-1 Ligand Selected from an Encoded Self-Assembling Chemical Library
-
We describe the construction of a DNA-encoded chemical library comprising 148 135 members, generated through the self-assembly of two sub-libraries, containing 265 and 559 members, respectively. The library was designed to contain building blocks potentially capable of forming covalent interactions with target proteins. Selections performed with JNK1, a kinase containing a conserved cysteine residue close to the ATP binding site, revealed the preferential enrichment of a 2-phenoxynicotinic acid moiety (building block A82) and a 4-(3,4-difluorophenyl)-4-oxobut-2-enoic acid moiety (building block B272). When the two compounds were joined by a short PEG linker, the resulting bidentate binder (A82-L-B272) was able to covalently modify JNK1 in the presence of a large molar excess of glutathione (0.5 mm), used to simulate intracellular reducing conditions. By contrast, derivatives of the individual building blocks were not able to covalently modify JNK1 in the same experimental conditions. The A82-L-B272 ligand was selective over related kinases (BTK and GAK), which also contain targetable cysteine residues in the vicinity of the active site.
- Zimmermann, Gunther,Rieder, Ulrike,Bajic, Davor,Vanetti, Sara,Chaikuad, Apirat,Knapp, Stefan,Scheuermann, J?rg,Mattarella, Martin,Neri, Dario
-
-
Read Online
- Mono-acylation of symmetric diamines in the presence of water
-
Simply reacting equal equivalents of symmetric diamines with esters or carbonates in the presence of a suitable amount of water gave mono-acylated products in good to quantitative yields.
- Tang, Wei,Fang, Shiyue
-
-
Read Online
- Anion interaction with ferrocene-functionalised cyclic and open-chain polyaza and aza-oxa cycloalkanes
-
A family of ferrocene-functionalised receptors of different topologies have been used as receptors for anions. The compounds have been designed to contain both amine nitrogen and ether oxygen atoms and comprises from monoaza to pentaaza derivatives both open-chain (L1, L2, L3) or cyclic (L4, L5) and having from one to five ferrocenyl groups. Solution studies directed to determine the protonation constants of L1, L2 and L3 have been carried out in water (0.1 mol dm3 KNO3, 25 °C) and those of L4 and L5 in 1,4-dioxane-water (70:30 v/v, 0.1 mol dm-3 KNO3, 25 °C). The protonation behaviour of the receptors can be explained taking into account electrostatic considerations. Speciation studies in the presence of phosphate have been carried out in water for L', L2 and L3 and in dioxane-water for L4 and L5. Speciation studies have also been performed in the presence of ATP with L1, L2 and L3 in water. Selectivity of a mixture of receptors against a certain anion is discussed in terms of ternary diagrams. The shift of the redox potential of the ferrocenyl groups as a function of the pH has been studied. The difference between the oxidation potentials at basic and acidic pH has been determined experimentally and is compared with that theoretically predicted using an electrostatic model previously reported. The electrochemical shift in the presence of ATP and phosphate has been measured in water for L1, L2 and L3 and in the presence of phosphate and sulfate in 1,4-dioxane-water for L4 and L5 as a function of the pH. The electrochemical response found against those anions is quite poor with maximum cathodic shifts off. 30tO mV. The electrochemical response induced by HSO4 and H2PO4- has also been studied in acetonitrile solutions where a large cathodic shift for H2PO4- up to ca. 200 mV was found. The Royal Society of Chemistry 2000.
- Beer, Paul D.,Cadman, James,Lloris, Jose Manuel,Martinez-Manez, Ramoen,Soto, Juan,Pardo, Teresa,Dolores Marcos
-
-
Read Online
- Amphiphilic [5:1]- and [3:3]-hexakisadducts of C60
-
We have synthesized and characterized a variety of new amphiphilic hexakisadducts of C60 involving mixed octahedral [5:1]- and [3:3]-addition patterns. The [5:1]-adducts 3 and 13 contain five pairs of didodecyl or diethyl malonates as non-polar addends and, as their polar part, an extended bis(malonate) involving C14 and ethylene glycol chains and two biotin termini. For the first time, amphiphilic [3:3]-hexakisadducts have been prepared using the e,e,e-trisadduct 18, which contains a cyclo-[3]-octyl malonate addend, as the precursor. As polar groups, we used malonates featuring carboxy, amino, or peptide termini. The charge on the termini, which can range from zero up to sixfold positive or sixfold negative, can be built up by protonation or deprotonation. All the amphiphilic [3:3]-hexakisadducts are very soluble in water in their completely charged forms. Initial investigations on the aggregation properties of the amphiphilic [3:3]-hexakisadducts, conducted using transmission electron microscopy (TEM) and pulse-gradient spin echo (PGSE) NMR spectroscopy, reveal the pH-dependent formation of aggregates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Braun, Martin,Hartnagel, Uwe,Ravanelli, Elena,Schade, Boris,Boettcher, Christoph,Vostrowsky, Otto,Hirsch, Andreas
-
-
Read Online
- Dynamic multivalent interaction of phenylboronic acid functionalized dendrimers with vesicles
-
Over the past decade cyclodextrin vesicles were established as a versatile model for biological membranes since they can be easily modified with functional groups due to the spontaneous formation of host-guest complexes. In this article we report the inte
- Otremba, Tobias,Ravoo, Bart Jan
-
-
Read Online
- Practical synthesis of maleimides and coumarin-linked probes for protein and antibody labelling via reduction of native disulfides
-
The cellular tracking, detection and sensing of protein or antibody movement are important aspects to advance our understanding of biomolecular interactions and activity. Antibodies modified with fluorescent dyes are also valuable tools, especially in immunology research. We describe here a proof-of-principle study of a new water-soluble coumarin probe with a maleimide thiol-reacting unit to fluorescently tag biomolecules. Highlights include: (1) a convenient water-based preparation of N-substituted maleimides, (2) a one-pot preparation of activated maleimido-esters, and (3) a bio-conjugation protocol for the selenol-promoted reduction of native disulfide bonds and the 'site-specific' labelling of antibodies with no significant loss of activity.
- Song, Hong Y.,Ngai, Mun H.,Song, Zhen Y.,MacAry, Paul A.,Hobley, Jonathan,Lear, Martin J.
-
-
Read Online
- Functionalization of diameter-sorted semiconductive SWCNTs with photosensitizing porphyrins: Syntheses and photoinduced electron transfer
-
Covalent functionalization of diameter sorted SWCNTs with porphyrins (MP), and photochemistry to establish nanotube diameter-dependent charge separation efficiencies are reported. The MP-SWCNT(n,m) [M=2 H or Zn, and (n,m)=(7,6) or (6,5)] nanohybrids are c
- Das, Sushanta K.,Subbaiyan, Navaneetha K.,D'Souza, Francis,Sandanayaka, Atula S. D.,Zandler, Melvin E.,Ito, Osamu
-
p. 11388 - 11398,11
(2012)
-
Read Online
- Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy
-
Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known
- Schneider, Raphael,Schmitt, Frederic,Frochot, Celine,Fort, Yves,Lourette, Natacha,Guillemin, Francois,Mueller, Jean-Francois,Barberi-Heyob, Muriel
-
-
Read Online
- Synthesis of C-4 and C-7 triazole analogs of zanamivir as multivalent sialic acid containing scaffolds
-
The relative reactivities of C-4 and C-7 azides derived from zanamivir were compared in cycloaddition reactions with a panel of alkynes. All of the reactions proceeded efficiently with no observable differences between primary and secondary azides. Signif
- Lu, Yan,Gervay-Hague, Jacquelyn
-
-
Read Online
- A Supramolecular-Based Dual-Wavelength Phototherapeutic Agent with Broad-Spectrum Antimicrobial Activity Against Drug-Resistant Bacteria
-
With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supra
- Chen, Daijie,Chen, Guo-Rong,Dong, Xiaojing,He, Xiao-Peng,Hu, Xi-Le,Kwon, Nahyun,Li, Xingshu,Mai, Yiyong,Tang, Tingting,Tian, He,Xu, Fugui,Yan, Jiatao,Yoon, Juyoung,Yu, Zhi-Hao
-
-
Read Online
- Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme
-
Over the past 20 years, the generation of functional RNAs by in vitro selection has become a standard technique. Apart from aptamers for simple binding of defined ligands, also RNAs for catalysis of chemical reactions have been selected. In the latter case, a key step often is the conjugation of one of the two reactants to the library, requiring suitable strategies for terminal or internal RNA functionalization. With the aim of selecting a ribozyme for deamination of cytidine, we have set up a selection scheme involving the attachment of the cytidine acting as deamination substrate to the 3'-terminus of the RNAs in the library, and library immobilization. Here, we report the synthesis of a bifunctional cytidine derivative suitable for conjugation to RNA and linkage of the conjugated library to a streptavidine-coated surface. Successful conjugation of the cytidine derivative to the 3'-terminus of a model RNA is demonstrated.
- Rublack, Nico,Mueller, Sabine
-
-
Read Online
- Lipid fluorination enables phase separation from fluid phospholipid bilayers
-
To probe the effect of lipid fluorination on the formation of lipid domains in phospholipid bilayers, several new fluorinated and non-fluorinated synthetic lipids were synthesised, and the extent of phase separation of these lipids from phospholipid bilayers of different compositions was determined. At membrane concentrations as low as 1% mol/mol, both fluorinated and non-fluorinated lipids were observed to phase separate from a gel-phase (solid ordered) phospholipid matrix, but bilayers in a liquid disordered state caused no phase separation; if the gel-phase samples were heated above the transition temperature, then phase separation was lost. We found incorporation of perfluoroalkyl groups into the lipid enhanced phase separation, to such an extent that phase separation was observed from cholesterol containing bilayers in the liquid ordered phase. The Royal Society of Chemistry 2006.
- Webb, Simon J.,Greenaway, Kevin,Bayati, Marzieh,Trembleau, Laurent
-
-
Read Online
- Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkers
-
Conjugation of therapeutics to human serum albumin (HSA) using bromomaleimides represents a promising platform for half-life extension. We show here that the Cys-34 crevice substantially reduces the rate of serum stabilising maleimide hydrolysis in these
- Wall, Archie,Nicholls, Karl,Caspersen, Mikael B.,Skrivergaard, Stig,Howard, Kenneth A.,Karu, Kersti,Chudasama, Vijay,Baker, James R.
-
-
Read Online
- Luminescent rare-earth complex covalently modified single-walled carbon nanotubes: Design, synthesis, and DNA sequence-dependent red luminescence enhancement
-
A novel luminescent Eu3+-complex functionalized single-walled carbon nanotube (SWNT) was constructed by covalent linkage through a diaminotriethylene glycol linker. TGA, FT-IR, and SEM demonstrated successful attachment of the Eu3+-complex onto the SWNT surface. Spectroscopic methods showed that the SWNT-Eu3+ complex is highly luminescent and DNA can further enhance the red luminescence, and the enhancement depends on DNA sequence and form. The order of the enhancement follows: AT alternative dsDNA > nonalternative AT dsDNA > GC dsDNA > ssDNA dA > ssDNA dT > ssDNA (GT)20.
- Zhao, Chao,Song, Yujun,Qu, Konggang,Ren, Jinsong,Qu, Xiaogang
-
-
Read Online
- A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells
-
A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine induced IgG antibodies that exhibited similar binding to human breast tumor cells.
- Glaffig, Markus,Stergiou, Natascha,Hartmann, Sebastian,Schmitt, Edgar,Kunz, Horst
-
-
Read Online
- Discovery of Mycobacterium tuberculosis Rv3364c-Derived Small Molecules as Potential Therapeutic Agents to Target SNX9 for Sepsis
-
The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the 12WLVSKF17 motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficki
- Lee, Daeun,Lee, Eunbi,Jang, Sein,Kim, Kyungmin,Cho, Euni,Mun, Seok-Jun,Son, Wooic,Jeon, Hye-In,Kim, Hyo Keun,Jeong, Young Jin,Lee, Yuno,Oh, Ji Eun,Yoo, Hye Hyun,Lee, Youngbok,Min, Sun-Joon,Yang, Chul-Su
-
p. 386 - 408
(2022/01/20)
-
- LIGAND DRUG CONJUGATES AND MODIFIED BET INHIBITORS
-
A ligand drug conjugate comprising a) a targeting ligand; b) a cleavable bridge; and a bromodomain and extraterminal (BET) inhibitor is provided. The targeting ligand may comprise a cancer targeting ligand. The BET inhibitor may comprise I-BET762, (+)-JQ1, MS417, OXT015, (2), RVX-208, (3), OXFBD02, OXFBD03, I-BET151, (4), PFI-1, I-BET726, MS436, XD14 or a modified BET inhibitor. Modified BET inhibitors are also provided, including RT48 ((S) -2- (6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f] [1,2,4] triazolo [4,3-a] [1,4] diazepin-4-yl)-1-(4-(dimethylamino) piperidin-1-yl) ethan-1-one) and RT53 ((S) -2- (6- (4-chlorophenyl) -8-methoxy-1-methyl-4H-benzo[f] [1,2,4] triazolo [4,3-a] [1,4] diazepin-4-yl) -N-(4- (4- (dimethylamino) piperidin-1-yl) phenyl) acetamide). A pro-drug of a BET inhibitor is also provided. A method of preparing a ligand drug conjugate according to the invention is also provided. The method comprises i) functionalising a BET inhibitor with a tertiary amine to form a modified BET inhibitor according to the invention; ii) bonding the modified BET inhibitor formed in step i) to a cleavable bridge; and iii) bonding the cleavable bridge bound to the modified BET inhibitor formed in step ii) to a targeting ligand. A ligand drug conjugate according to the invention for use as a medicament is also provided.
- -
-
Page/Page column 9-10
(2021/07/17)
-
- COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING CALCIUM ION HOMEOSTASIS
-
The present disclosure relates to compounds that are capable of modulating calcium ion homeostasis and treating disorders related thereto. The disclosure further relates to methods of making the aforementioned compounds.
- -
-
Page/Page column 71
(2021/08/20)
-
- Improved Stabilities of Labeling Probes for the Selective Modification of Endogenous Proteins in Living Cells and In Vivo
-
To date, various affinity-based protein labeling probes have been developed and applied in biological research to modify endogenous proteins in cell lysates and on the cell surface. However, the reactive groups on the labeling probes are also the cause of
- Lin, Kuan-Yu,Hin Lam, Chak,Lin, Xin-Hui,Hsu, Jung-I,Fan, Syuan-Yun,Gupta, Nitesh K.,Lin, Yu-Chun,Khoon Tee, Boon,Li, Jui-Ping,Chen, Jen-Kun,Tan, Kui-Thong
-
supporting information
p. 937 - 948
(2021/03/16)
-
- A Color-Shifting Near-Infrared Fluorescent Aptamer–Fluorophore Module for Live-Cell RNA Imaging
-
Fluorescent light-up RNA aptamers (FLAPs) have become promising tools for visualizing RNAs in living cells. Specific binding of FLAPs to their non-fluorescent cognate ligands results in a dramatic fluorescence increase, thereby allowing RNA imaging. Here, we present a color-shifting aptamer-fluorophore system, where the free dye is cyan fluorescent and the aptamer-dye complex is near-infrared (NIR) fluorescent. Unlike other reported FLAPs, this system enables ratiometric RNA imaging. To design the color-shifting system, we synthesized a series of environmentally sensitive benzopyrylium-coumarin hybrid fluorophores which exist in equilibrium between a cyan fluorescent spirocyclic form and a NIR fluorescent zwitterionic form. As an RNA tag, we evolved a 38-nucleotide aptamer that selectively binds the zwitterionic forms with nanomolar affinity. We used this system as a light-up RNA marker to image mRNAs in the NIR region and demonstrated its utility in ratiometric analysis of target RNAs expressed at different levels in single cells.
- Zhang, Jingye,Wang, Lu,J?schke, Andres,Sunbul, Murat
-
supporting information
p. 21441 - 21448
(2021/08/23)
-
- Polyethylene glycol coupling medicine as well as preparation method and application thereof
-
The invention relates to the technical field of medicines, relates to a polyethylene glycol coupled drug as well as a preparation method and an application thereof, and in particular relates to a polyethylene glycol coupled drug as shown in a formula I or pharmaceutically acceptable salt thereof. The invention also relates to a preparation method of the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof, and the application of the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof in preparation of drugs.
- -
-
Paragraph 1231-1234
(2021/05/29)
-
- JNK Inhibitor. Pharmaceutical compositions and uses thereof
-
Provided herein are compounds represented by the following formula (I), racemates, stereoisomers, tautomers, isotopically labels, solvates, polymorphs, nitrogen oxides or pharmaceutically acceptable salts thereof, which can be used as JNK inhibitors. A method for preparing a compound represented by formula (I), a pharmaceutical composition comprising a compound represented by formula (I), and (I), for the preparation of a medicament for the treatment of a disease treatable by inhibition JNK activity.
- -
-
Paragraph 0161-0164
(2021/11/27)
-
- BIFUNCTIONAL AGENTS FOR PROTEIN RECRUITMENT AND/OR DEGRADATION
-
The disclosure relates to new compounds, including bifunctional compounds, to be used as modulators of ubiquitination for targeted protein degradation.
- -
-
Paragraph 0242
(2021/06/26)
-
- Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35
-
FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35 contains a cysteine, C106, adjacent to the rapamycin binding pocket, providing an opportunity to develop targeted covalent inhibitors of Plasmodium FKBP35. Here, we synthesize inhibitors of FKBP35, show that they directly bind FKBP35 in a model cellular setting, selectively covalently modify C106, and exhibit antiplasmodium activity in blood-stage cultured parasites.
- Atack, Thomas C.,Raymond, Donald D.,Blomquist, Christa A.,Pasaje, Charisse Flerida,McCarren, Patrick R.,Moroco, Jamie,Befekadu, Henock B.,Robinson, Foxy P.,Pal, Debjani,Esherick, Lisl Y.,Ianari, Alessandra,Niles, Jacquin C.,Sellers, William R.
-
supporting information
p. 2131 - 2138
(2020/12/17)
-
- NOVEL MOLECULES FOR TARGETING RIBOSOMES AND RIBOSOME-INTERACTING PROTEINS, AND USES THEREOF
-
Molecule having the structural formula (I): (I) for use as targeting probe of translating ribosomes and ribosome-interacting proteins.
- -
-
Page/Page column 30-32
(2020/02/06)
-
- COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
-
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a -S(=0)(=N-)- functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
- -
-
Page/Page column 154
(2020/09/03)
-
- Inverse Electron-Demand Diels-Alder Bioconjugation Reactions Using 7-Oxanorbornenes as Dienophiles
-
Oligonucleotides, peptides, and peptide nucleic acids incorporating 7-oxanorbornene as a dienophile were reacted with tetrazines linked to either a peptide, d-biotin, BODIPY, or N-acetyl-d-galactosamine. The inverse electron-demand Diels-Alder (IEDDA) cycloaddition, which was performed overnight at 37 °C, in all cases furnished the target conjugate in good yields. IEDDA reactions with 7-oxanorbornenes produce a lower number of stereoisomers than that of IEDDA cycloadditions with other dienophiles.
- Agramunt, Jordi,Ginesi, Rebecca,Grandas, Anna,Pedroso, Enrique
-
p. 6593 - 6604
(2020/07/14)
-
- Rapid and Selective Labeling of Endogenous Transmembrane Proteins in Living Cells with a Difluorophenyl Ester Affinity-Based Probe
-
The long-term stability of affinity-based protein labeling probes is crucial to obtain reproducible protein labeling results. However, highly stable probes generally suffer from low protein labeling efficiency and pose significant challenges when labeling low abundance native proteins in living cells. In this paper, we report that protein labeling probes based on an ortho-difluorophenyl ester reactive module exhibit long-term stability in DMSO stock solution and aqueous buffer, yet they can undergo rapid and selective labeling of native proteins. This novel electrophile can be customized with a wide range of different protein ligands and is particularly well-suited for the labeling and imaging of transmembrane proteins. With this probe design, the identity and relative levels of basal and hypoxia-induced transmembrane carbonic anhydrases were revealed by live cell imaging and in-gel fluorescence analysis. We believe that the extension of this difluorophenyl ester reactive module would allow for the specific labeling of various endogenous membrane proteins, facilitating in-depth studies of their distribution and functions in biological processes.
- Chan, Hsin-Ju,Lin, Xin-Hui,Fan, Syuan-Yun,Ru Hwu, Jih,Tan, Kui-Thong
-
supporting information
p. 3416 - 3420
(2020/10/02)
-
- Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds
-
Among other aspects, provided herein are multi-arm polymeric prodrug conjugates of pemetrexed-based compounds. Methods of preparing such conjugates as well as methods of administering the conjugates are also provided. Upon administration to a patient, release of the pemetrexed-based compound is achieved.
- -
-
Page/Page column 25
(2020/08/30)
-
- Mild deprotection of the: N-tert -butyloxycarbonyl (N -Boc) group using oxalyl chloride
-
We report a mild method for the selective deprotection of the N-Boc group from a structurally diverse set of compounds, encompassing aliphatic, aromatic, and heterocyclic substrates by using oxalyl chloride in methanol. The reactions take place under room temperature conditions for 1-4 h with yields up to 90percent. This mild procedure was applied to a hybrid, medicinally active compound FC1, which is a novel dual inhibitor of IDO1 and DNA Pol gamma. A broader mechanism involving the electrophilic character of oxalyl chloride is postulated for this deprotection strategy. This journal is
- Awuah, Samuel G.,George, Nathaniel,Ofori, Samuel,Parkin, Sean
-
p. 24017 - 24026
(2020/07/23)
-
- Efficient Innate Immune Killing of Cancer Cells Triggered by Cell-Surface Anchoring of Multivalent Antibody-Recruiting Polymers
-
Binding of monoclonal antibodies (mAbs) onto a cell surface triggers antibody-mediated effector killing by innate immune cells through complement activation. As an alternative to mAbs, synthetic systems that can recruit endogenous antibodies from the blood stream to a cancer cell surface could be of great relevance. Herein, we explore antibody-recruiting polymers (ARPs) as a novel class of immunotherapy. ARPs consist of a cell-binding motif linked to a polymer that contains multiple small molecule antibody-binding motifs along its backbone. As a proof of concept, we employ a lipid anchor that inserts into the phospholipid cell membrane and make use of a polymeric activated ester scaffold onto which we substitute dinitrophenol as an antibody-binding motif. We demonstrate that ARPs allow for high avidity antibody binding and drive antibody recruitment to treated cells for several days. Furthermore, we show that ARP-treated cancer cells are prone to antibody-mediated killing through phagocytosis by macrophages.
- Uvyn, Annemiek,De Coen, Ruben,Gruijs, Mandy,Tuk, Cees W.,De Vrieze, Jana,van Egmond, Marjolein,De Geest, Bruno G.
-
supporting information
p. 12988 - 12993
(2019/08/01)
-
- Cell surface clicking of antibody-recruiting polymers to metabolically azide-labeled cancer cells
-
Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue. In this context, recruitment of endogenous antibodies to the cancer cell surface could be a viable alternative to the use of monoclonal antibodies. We report on antibody-recruiting polymers containing multiple antibody-binding hapten motifs and cyclooctynes that can covalently conjugate to azides introduced onto the glycocalyx of cancer cells by metabolic labeling with azido sugars.
- Uvyn, Annemiek,De Coen, Ruben,De Wever, Olivier,Deswarte, Kim,Lambrecht, Bart N.,De Geest, Bruno G.
-
supporting information
p. 10952 - 10955
(2019/09/18)
-
- A MedChem toolbox for cereblon-directed PROTACs
-
A modular chemistry toolbox was developed for cereblon-directed PROTACs. A variety of linkers was attached to a CRBN ligand via the 4-amino position of pomalidomide. We used linkers of different constitution to modulate physicochemical properties. We equipped one terminus of the linker with a set of functional groups, e.g. protected amines, protected carboxylic acids, alkynes, chloroalkanes, and protected alcohols, all of which are considered to be attractive for PROTAC design. We also highlight different opportunities for the expansion of the medicinal chemists' PROTAC toolbox towards heterobifunctional molecules, e.g. with biotin, fluorescent, hydrophobic and peptide tags.
- Steinebach, Christian,Sosi?, Izidor,Lindner, Stefanie,Bricelj, Ale?a,Kohl, Franziska,Ng, Yuen Lam Dora,Monschke, Marius,Wagner, Karl G.,Kr?nke, Jan,Gütschow, Michael
-
supporting information
p. 1037 - 1041
(2019/06/27)
-
- COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
-
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
- -
-
Page/Page column 162
(2019/01/21)
-
- Evaluation of linker length effects on a BET bromodomain probe
-
Fueled by the therapeutic potential of the epigenetic machinery, BET bromodomains have seen high interest as drug targets. Herein, we introduce different linkers to a BET bromodomain benzodiazepine ligand (I-BET762) to gauge its implications in the develo
- Traquete, Rui,Henderson, Elizabeth,Picaud, Sarah,Cal, Pedro M. S. D.,Sieglitz, Florian,Rodrigues, Tiago,Oliveira, Rudi,Filippakopoulos, Panagis,Bernardes, Gon?alo J. L.
-
supporting information
p. 10128 - 10131
(2019/08/30)
-
- Synthesis process of Boc-1-amino-3,6-dioxa-1,8-octanediamine
-
The invention belongs to the technical field of preparation of Boc-1-amino-3,6-dioxa-1,8-octanediamine, and particularly relates to a synthesis process of the Boc-1-amino-3,6-dioxa-1,8-octanediamine.The synthesis process comprises the following steps: 3,6-dioxa-1,8-octanediamine and tert-butoxyacyl chloride are used as raw materials to carry out substitution reaction in one step, wherein the solvent used in the reaction is selected from a mixed solvent of any two of acetonitrile, toluene, diethyl ether, cyclohexane, n-ethane and chloroform. The synthetic process of the Boc-1-amino-3,6-dioxa-1,8-octanediamine has simple reaction route and short reaction time; a target product with high yield and high purity can be obtained without complex purification and separation processes, the operation is simple, and the method is suitable for industrial scale-up production.
- -
-
Paragraph 0025-0076
(2019/06/12)
-
- Facile fabrication of branched-chain carbohydrate chips for studying carbohydrate-protein interactions by QCM biosensor
-
A novel approach for fabricating branched-chain (BC) carbohydrate chips to study carbohydrate-protein interactions using Quartz Crystal Microbalance (QCM) biosensor was developed. This approach utilizes functional alkynyl-branch molecule modified chip surfaces, which through the terminal alkynyl group for covalent linking of unprotected azide-carbohydrates. The unprotected azide-carbohydrates were syhthesized in one-step using 2-azido-1,3-dimethyl-imidazolinium as catalyst, avoiding complex chemical modifications. Additionally, the branch surface modified with the carbohydrates not only supplies more specific binding site but also reveals significant cluster effect. To exemplify the sugar cluster effect on BC carbohydrate chips, BC Galactose and Mannose chips prepared in this work were used to determine carbohydrate-lectin interactions using QCM biosensor. The results clearly showed that BC chip significantly improves the detection sensitivity compared with the straight-chain (SC) chip. More importantly, the BC galactose chip sensitivity was enhanced 40% compared with the SC galactose chip.
- Lu, Yuchao,Song, Siyu,Hou, Chenxi,Pang, Shuang,Li, Xueming,Wu, Xiaowen,Shao, Chen,Pei, Yuxin,Pei, Zhichao
-
supporting information
p. 65 - 68
(2017/09/06)
-
- A Combined Photochemical and Multicomponent Reaction Approach to Precision Oligomers
-
We introduce the convergent synthesis of linear monodisperse sequence-defined oligomers through a unique approach, combining the Passerini three-component reaction (P-3CR) and a Diels–Alder (DA) reaction based on photocaged dienes. A set of oligomers is prepared resting on a Passerini linker unit carrying an isocyano group for chain extension by P-3CR and a maleimide moiety for photoenol conjugation enabling a modular approach for chain growth. Monodisperse oligomers are accessible in a stepwise fashion by switching between both reaction types. Employing sebacic acid as a core unit allows the synthesis of a library of symmetric sequence-defined oligomers. The oligomers consist of alternating P-3CR and photoblocks with molecular weights up to 3532.16 g mol?1, demonstrating the successful switching from P-3CR to photoenol conjugation. In-depth characterization was carried out including size-exclusion chromatography (SEC), high-resolution electrospray ionization mass spectrometry (ESI-MS) and NMR spectroscopy, evidencing the monodisperse nature of the precision oligomers.
- Konrad, Waldemar,Bloesser, Fabian R.,Wetzel, Katharina S.,Boukis, Andreas C.,Meier, Michael A. R.,Barner-Kowollik, Christopher
-
supporting information
p. 3413 - 3419
(2018/02/09)
-
- NOVEL CHLORIN E6-CURCUMIN DERIVATIVES, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME FOR TREATMENT OF CANCER
-
The present invention relates to novel chlorine e6-curcumin derivatives, a preparation method thereof for the treatment of cancer, and in particularly, novel compounds were prepared by using different linkers such as hydrophobic and hydrophilic linkers to conjugate chlorine e6 to curcumin, the compounds under investigation showed excellent photophysical properties, stability, and anticancer activity.
- -
-
Paragraph 160; 161; 162; 163
(2019/01/10)
-
- LINKER-DRUG AND ANTIBODY-DRUG CONJUGATE (ADC) EMPLOYING THE SAME
-
A linker-drug represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof is provided. In formula (I), C is a conjugator, L is a linker unit, D is a toxin unit, and n is an integer ranging from 1 to 4. The structure of the conjugator is represented by formula (II). In formula (II), X is a leaving group, each of R1 and R2 is independently a single bond or —NH—, and Z is substituted aryl, heteroaryl, linear alkyl, cycloalkyl, heterocycloalkyl, or a combination thereof. The antibody is conjugated to the linker unit through a cysteine residue of the antibody. An antibody-drug conjugate (ADC) employing the above linker-drug is also provided.
- -
-
Paragraph 0116; 0117; 0220
(2018/07/05)
-
- Selective radiolabelling with 68Ga under mild conditions: A route towards a porphyrin PET/PDT theranostic agent
-
A theranostic conjugate for use as a positron emission tomography (PET) radiotracer and as a photosensitiser for photodynamic therapy (PDT) has been synthesised. A water-soluble porphyrin was coupled with the bifunctional chelate, H4Dpaa.ga. This conjugate is capable of rapid 68Ga complexation under physiological conditions; with 93% and 80% radiochemical yields achieved, at pH 4.5 and pH 7.4 respectively, in 15 min at 25 °C. Photocytotoxicity was evaluated on HT-29 cells and showed the conjugate was capable of >50% cell death at 50 μM upon irradiation with light, while causing minimal toxicity in the absence of light (>95% cell survival).
- Yap, Steven Y.,Price, Thomas W.,Savoie, Huguette,Boyle, Ross W.,Stasiuk, Graeme J.
-
supporting information
p. 7952 - 7954
(2018/07/25)
-
- An amine protecting group deprotectable under nearly neutral oxidative conditions
-
The 1,3-dithiane-based dM-Dmoc group was studied for the protection of amino groups. Protection was achieved under mild conditions for aliphatic amines, and under highly reactive conditions for the less reactive arylamines. Moderate to excellent yields were obtained. Deprotection was performed by oxidation followed by treating with a weak base. The yields were good to excellent. The new amino protecting group offers a different dimension of orthogonality in reference to the commonly used amino protecting groups in terms of deprotection conditions. It is expected to allow a collection of transformations to be carried out on the protected substrates that are unattainable using any known protecting groups.
- Shahsavari, Shahien,McNamara, Chase,Sylvester, Mark,Bromley, Emily,Joslin, Savannah,Lu, Bao-Yuan,Fang, Shiyue
-
p. 1750 - 1757
(2018/08/21)
-
- Synthesis of novel 2H-indazole analogues via the Davis-Beirut reaction and conjugation onto magnetic nanoparticles
-
Methods for the construction of C3-amino substituted 2H-indazole motifs are scarce. While the Davis-Beirut reaction proved useful and versatile in the construction of alkoxy- and thia- C3-substituted 2H-indazoles under mild basic conditions, the same succ
- El-Dakdouki, Mohammad H.,Hussein, AbdulSattar,Abdallah, Hiba,Shatila, Rania,Mouneimne, Youssef
-
p. 5769 - 5777
(2017/09/05)
-
- NEW MOLECULES FOR ISOLATION OF POLYRIBOSOMES, RIBOSOMES, USES AND KITS THEREOF
-
Molecules of general Formula (I): able to bind to native polyribosomes engaged in active protein synthesis. The disclosure relates also to the use of the molecules of general Formula (I) for isolating at least one active ribosome from a biological sample, and for ribosome profiling, as well as kits for isolating at least one active ribosome from a biological sample.
- -
-
Page/Page column 47-48
(2017/02/09)
-
- Preparation method of 2-(2-(2-amidogen ethyoxyl) ethyoxyl) ethyl carbamic acid tert-butyl ester
-
The invention relates to a preparation method of a 2-(2-(2-amidogen ethyoxyl) ethyoxyl) ethyl carbamic acid tert-butyl ester. The method comprises the following steps of reacting ethylene glycol and haloacetonitrile at the temperature of 0 to 60 DEG C under the existence of alkali, and obtaining 1,6-dicyano-2,5-dioxa hexane in a formula (I); carrying out reduction reaction on the 1,6-dicyano-2,5-dioxa hexane in the formula (I) in an organic solvent, and obtaining 1,8-diamido-3,6-dioxa octane in a formula (II); carrying out Boc monoprotection reaction on the 1,8-diamido-3,6-dioxa octane in the formula (II) and a di-tert-butyl dicarbonate ester in an organic solvent, and obtaining the 2-(2-(2-amidogen ethyoxyl) ethyoxyl) ethyl carbamic acid tert-butyl ester in a formula (III), wherein a reaction route is as shown in the below figure, and X is chlorine, bromine or iodine. The preparation method provided by the invention is less in operation steps and simple and convenient, not only can overcome the defect that the 1,8-diamido-3,6-dioxa octane obtained through a traditional Staudinger reduction method contains water, but also can avoid the insecurity of azide, and is suitable for industrial production.
- -
-
Paragraph 0049; 0053; 0054; 0055
(2017/08/29)
-
- Specific fluorescence labeling of target proteins by using a ligand-4-azidophthalimide conjugate
-
We herein propose a simple affinity-labeling method using a ligand-4-azidophthalimide (AzPI) conjugate. As a proof of concept, we show that two different ligand-AzPI conjugates enabled highly specific fluorescence labeling of their individual target proteins even in crude cell lysates. This method was also applied to label endogenous target proteins inside living cells.
- Chiba, Kosuke,Asanuma, Miwako,Ishikawa, Minoru,Hashimoto, Yuichi,Dodo, Kosuke,Sodeoka, Mikiko,Yamaguchi, Takao
-
supporting information
p. 8751 - 8754
(2017/08/10)
-
- ALKYNYL INDAZOLE DERIVATIVE AND USE THEREOF
-
The main object of the present invention is to provide a novel compound which has a VEGF receptor tyrosine kinase inhibitory activity and is useful as an active ingredient for the treatment of diseases accompanying angiogenesis or edema, for example, age-related macular degeneration or the like. The present invention includes, for example, an alkynyl indazole derivative represented by the following general formula (I), a pharmaceutical acceptable salt thereof, and a medicine containing thereof.
- -
-
Paragraph 0266; 0267
(2017/02/24)
-
- IRON COMPLEXING AGENT AND USES THEREOF IN THE TREATMENT AND PREVENTION OF COLORECTAL CANCER
-
A complex comprising a non-absorbable portion attached to an iron chelator moiety, a composition comprising the complex and the use of the complex in the treatment of colorectal cancer. In one embodiment the non-absorbable portion is a polymer such as a polysaccharide, including chitosan, chitin, cellulose or pectin. In one embodiment the iron chelator moiety comprises at least one functional group selected from catechol, hydroxamate or carboxylate, or any combination thereof.
- -
-
Paragraph 0066-0067
(2016/10/31)
-
- Cosmetic composition for skin whitening with peptide from golden silkworm
-
The present invention relates to a skin whitening cosmetic composition comprising a peptide derived from golden silkworm as an effective component. The cosmetic composition of the present invention comprises a compound which is prepared by the PEGylation
- -
-
Paragraph 0083; 0084; 0085
(2017/06/03)
-
- Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development
-
The use of small molecules to regulate cellular levels of specific proteins is poised to become a powerful technique in the coming years. Critical to the success of any project utilizing such an approach will be the ability to synthesize libraries of candidate small molecules for testing in cellular systems. Herein, we describe a practical synthesis of a phthalimide-based scaffold, which can be easily diversified to make Cereblon-targeting PROTACs. We demonstrate the effectiveness of this approach by synthesizing a ‘PROTAC toolbox’ of four amines which can be coupled to inhibitors in a straightforward manner.
- Lohbeck, Jasmin,Miller, Aubry K.
-
supporting information
p. 5260 - 5262
(2016/10/30)
-
- Identification of Targets of the HIF-1 Inhibitor IDF-11774 Using Alkyne-Conjugated Photoaffinity Probes
-
We developed a hypoxia-inducible factor-1 (HIF-1) inhibitor, IDF-11774, as a clinical candidate for cancer therapy. To understand the mechanism of action of IDF-11774, we attempted to isolate target proteins of IDF-11774 using bioconjugated probes. Multifunctional chemical probes containing sites for click conjugation and photoaffinity labeling were designed and synthesized. After fluorescence and photoaffinity labeling of proteins, two-dimensional electrophoresis (2DE) was performed to isolate specific molecular targets of IDF-11774. Heat shock protein (HSP) 70 was identified as a target protein of IDF-11774. We revealed that IDF-11774 inhibited HSP70 chaperone activity by binding to its allosteric pocket, rather than the ATP-binding site in its nucleotide-binding domain (NBD). Moreover, IDF-11774 reduced the oxygen consumption rate (OCR) and ATP production, thereby increasing intracellular oxygen tension. This result suggests that the inhibition of HSP70 chaperone activity by IDF-11774 suppresses HIF-1α refolding and stimulates HIF-1α degradation. Taken together, these findings indicate that IDF-11774-derived chemical probes successfully identified IDF-11774's target molecule, HSP70, and elucidated the mode of action of IDF-11774 in inhibiting HSP70 chaperone activity and stimulating HIF-1α degradation in cancer cells.
- Ban, Hyun Seung,Naik, Ravi,Kim, Hwan Mook,Kim, Bo-Kyung,Lee, Hongsub,Kim, Inhyub,Ahn, Heechul,Jang, Yerin,Jang, Kyusik,Eo, Yumi,Song, Kyung Bin,Lee, Kyeong,Won, Misun
-
p. 1911 - 1920
(2016/09/04)
-
- ALKYNES AND METHODS OF REACTING ALKYNES WITH 1,3-DIPOLE-FUNCTIONAL COMPOUNDS
-
1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also di
- -
-
Paragraph 0100
(2016/06/28)
-
- Reversible covalent linkage of functional molecules
-
The present invention relates to the use of a compound containing a moiety of formula (I) as a reagent for linking a compound of formula R1—H which comprises a first functional moiety of formula F1 to a second functional moiety of fo
- -
-
Page/Page column 62; 63
(2016/04/26)
-
- POLYCYCLIC EPOXIDES AND COMPOSITIONS THEREOF WITH ANTI-CANCER ACTIVITIES
-
The present technology provides polycyclic epoxides of Formula I, compositions comprising such expoxides and methods of using such epoxides. In particular, these compounds are useful for inhibiting cancer cell proliferation and tumor angiogenesis or treating ovarian, breast, prostate, liver, pancreatic, and colon cancers, as well as leukemia.
- -
-
Paragraph 0257-0259
(2016/12/01)
-
- Flow-mediated synthesis of Boc, Fmoc, and Dd iv monoprotected diamines
-
A series of monoprotected aliphatic diamines (21 examples) were synthesized via continuous flow methods. The carbamates and enamines were obtained in 45-91% yields using a 0.5 mm diameter PTFE tubular flow reactor. Using readily accessible protecting group precursors, the procedure serves as an attractive alternative to existing batch-mode synthetic routes by providing direct, multigram access to N-Boc-, N-Fmoc-, and N-Ddiv-protected compounds with productivity indexes of 1.2-3.6 g/h.
- Jong, Thingsoon,Bradley, Mark
-
supporting information
p. 422 - 425
(2015/03/03)
-
- Late stage modification of receptors identified from dynamic combinatorial libraries
-
Small molecule receptors are attractive potential sensors of post-translational modifications, including methylated lysine and methylated arginine. Using dynamic combinatorial chemistry (DCC), our lab previously identified a suite of receptors that bind to Kme3 with a range of affinities ranging from low micromolar to high nanomolar, each with a unique selectivity for Kme3 over the lower methylation states. To enable these receptors to have broad application as Kme3 sensors, we have developed a method for their late-stage modification, which we used to synthesize biotinylated derivatives of A2B, A2D, and A2G in a single step. For our most attractive receptor for applications, A2N, we needed to develop an alternative method for its selective functionalization, which we achieved by "activating" the carboxylic acids on the constituent monomer A or N by pre-functionalizing them with glycine (Gly). Using the resulting Gly-A and Gly-N monomers, we synthesized the novel A2N variants A2Gly-N, Gly-A2N, and Gly-A2Gly-N, which enabled the late stage biotinylation of A2N wherever Gly was incorporated. Finally, we performed ITC and NMR binding experiments to study the effect that carboxylate spacing has on the affinity and selectivity of A2Gly-N and Gly-A2N for KmeX guests compared to A2N. These studies revealed the proximity of the carboxylates to play a complex role in the molecular recognition event, despite their positioning on the outside of the receptor.
- Pinkin, Nicholas K.,Power, Amanie N.,Waters, Marcey L.
-
supporting information
p. 10939 - 10945
(2015/11/17)
-
- Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations
-
A modular approach combining inverse electron-demand Diels-Alder coupling (DARinv) and oxime ligation expands the toolbox of bioorthogonal peptide chemistry. Applicability of versatile site-specific bifunctional building blocks is demonstrated
- H?rner,Uth,Avrutina,Frauendorf,Wiessler,Kolmar
-
supporting information
p. 11130 - 11133
(2015/07/07)
-
- Versatile bisethynyl[60]fulleropyrrolidine scaffolds for mimicking artificial light-harvesting photoreaction centers
-
Fullerene-based tetrads, triads, and dyads are presented in which [60]fulleropyrrolidine synthons are linked to an oligo(p-phenyleneethynylene) antenna at the nitrogen atom and to electron-donor phenothiazine (PTZ) and/or ferrocene (Fc) moieties at the ?±
- Kremer, Adrian,Bietlot, Emerance,Zanelli, Alberto,Malicka, Joanna M.,Armaroli, Nicola,Bonifazi, Davide
-
supporting information
p. 1108 - 1117
(2015/03/05)
-
